Cracking the sugar code: the secret language cells use

When it comes to communicating the fundamentals of life, DNA gets all the credit. Almost everyone is familiar with the distinctive double helix, an iconic structure that has been familiar ever since 1953 when Watson and Crick published the now-legendary article announcing its discovery.

But what about life’s other language? The code which has been all-too-often overlooked next to its older, more famous sibling? You may not have heard of it, but it is called ‘the sugar code’, and it has the potential to be used as a powerful, potentially life-saving tool.

We know that cells use the sugar code (or ‘glycome’, in more formal terms) to convey all kinds of vital information to each other, and also that these cryptic communications play a role in countless diseases ranging from food allergies to cancer. If we could only learn to understand the code, or perhaps even use it to ‘write’ to cells, the possibilities are endless. We could employ it to harness the regenerative powers of stem cells, for instance, to control disease and to develop new antibiotics. Unfortunately, this has proved to be a gargantuan task, and so far the secrets of this mysterious cellular language have remained frustratingly elusive.

But that could be beginning to change.

To illustrate the importance of this secret cellular language, we can turn to the miracle of conception. You might think that humans do most of the hard-work involved in baby-making, but a sperm cell would probably disagree. After an arduous pilgrimage through the acidic environment of the vagina and up the fallopian tube, the sperm finally reaches the egg. It must now navigate the ‘zona pellucida’, a thick forest of sugars encasing the egg cell. To do this, it has to be able to grab hold of a glycan on the cell surface, using a specified molecular tool which perfectly complements the shape of the sugar. Once one pioneering sperm cell has managed to do this, the shape of the other glycans surrounding the cell changes. This is a bit like changing the locks on a house, the keys that the rival sperm have will no longer fit the sugary branches, and they are blocked from gaining access to the cell, a situation which would cause all kinds of problems.

So, it’s certainly clear that the sugar code is important, but why is it such a tough nut for scientists to crack? The short answer is that this fiendish code is staggeringly complex.

By way of comparison, we can again consider DNA. The DNA code is made up of four letters. These can be sorted into different orders and combinations, but are always linked up into a straight line.

The sugar code, however, is a whole different ball game. For starters, instead of being comprised of four basic units, it is made up of twenty. And then there is the matter of shape. In order to properly understand this language, you have to be able to identify all of the subtle variations in the branched structures of the different sugars, and then try to interpret what they might mean. Not to mention the fact that while each cell inherits the same set of DNA instructions to work with, when it comes to their “sugar jackets” they are much more particular. Like celebrities on the red carpet, no two cell types would dream of being caught in the same outfit.

So how are scientists taking on this task? A lot of important work has been done by chemists, isolating individual sugars and breaking them apart in order to better understand how they are structured. Researchers are also trying to figure out which specific molecular tools can grab onto which sugars. To do this, they fix glycans onto a surface and wash them with a solution of molecules. It is then a case of checking which tools have successfully latched onto which sugars.

If we can become sugar-literate the possibilities are truly endless. One exciting avenue of research is stem cells. A scientist called Kamil Godula at the University of California has found that bathing stem cells in specific sugars is an effective way of influencing their development towards becoming different cell types. This technique holds a lot of promise for the field of regenerative medicine. If we could manage to control the development of stem cells like this in living organisms, there is massive potential to help people who have suffered damage to various organs through disease or injury.

After all these years of neglect, it turns out that life’s alternative language might be pretty important after all.

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